nanoIMPAC: Monitoring immune toxicities and immune evasion in lung cancer

Immune checkpoint inhibition (ICI) has achieved impressive improvements in progression-free and overall survival of a small, but significant fraction of patients with lung cancer. However, a large proportion of patients do not benefit from ICI, due to ICI-induced immune toxicities that lead to treatment stop, additional patient sickness and increased requirements for care. It is currently not possible to monitor the immune response in ICI treated patients, or detect early the onset of immune toxicities. Patients receiving ICI also often show only a short-term treatment response before the disease continues to progress. Although not fully understood, lung cancer progression during ICI treatment is thought to be driven by immune evasion of the tumour. Similarly, tumour recurrence after curative surgery with or without adjuvant ICI in early stage disease is common and associated with immune evasion. As current diagnostics focuses on profiling the tumour, immune evasion is often detected late, contributing to the very low 5-year survival rates of lung cancer. To address these negative consequences of ICI and to improve therapeutic effectiveness, we have developed a nanotechnology-enabled integrated multiplex pillar array chip (nanoIMPAC) for detecting immune toxicities in ICI in cancer patients by profiling a panel of circulating cytokines in blood. We have shown the role of small extracellular vesicle (sEV) cytokines in tumour immune evasion and cancer-associated sEVs in tumour recurrence. This project will combine nanoIMPAC with these biomarker signatures as a novel blood-based screening technology, to detect for early immune toxicities in ICI treated patients, screen for immune evasion, and tumour recurrence. This project will provide fundamental insights into the immune modulation effects of ICI and tumour response, and the mechanisms of immune evasion in lung cancer, providing clinical information to support treatment in precision oncology.